2020 Virtual AIChE Annual Meeting
(157z) Self-Assembled Cgamp-Sting?tm Signaling Complex As a Bioinspired Platform for Cgamp Delivery
Authors
Yanpu He - Presenter, MIT
Celestine Hong, MIT
Emily Yan, MIT
Samantha Fletcher, Massachusetts Institute of Technology
Ge Zhu, Northeastern University
Mengdi Yang, Northeastern University
Xin Sun, Northeastern University
Yingzhong Li, Synthetic Biological Center, MIT
Jiahe Li, Massachusetts Institute of Technology
Darrell Irvine, MIT
Paula T. Hammond, MIT
The stimulator of interferon (IFN) genes (STING) pathway constitutes a highly important part of immune responses against various cancers and infections. Consequently, administration of STING agonists such as cyclic GMP-AMP (cGAMP) has been identified as a promising approach to target these diseases. In cancer cells, STING signaling is frequently impaired by epigenetic silencing of STING; hence, conventional delivery of only its agonist cGAMP may be insufficient to trigger STING signaling. In this work, while expression of STING lacking the transmembrane (TM) domain is known to be unresponsive to STING agonists and is dominant negative when coexpressed with the full-length STING inside cells, we observed that the recombinant TM-deficient STING protein complexed with cGAMP could effectively trigger STING signaling when delivered in vitro and in vivo, including in STING-deficient cell lines. Thus, this bio-inspired method using TM-deficient STING may present a new and universally applicable platform for cGAMP delivery.